INTRODUCTION: Within oncology research, there is a high effort for new approaches to prevent and treat cancer as a life-threatening disease. Specific plant species that adapt to harsh conditions may possess unique properties that may be utilized in the management of cancer. HYPOTHESIS: Chokeberry fruit is rich in secondary metabolites with anti-cancer activities potentially useful in cancer prevention and treatment. AIMS OF THE STUDY AND METHODS: Based on mentioned hypothesis, the main goal of our study was to evaluate the antitumor effects of dietary administered Aronia melanocarpa L. fruit peels (in two concentrations of 0.3 and 3% [w/w]) in the therapeutic syngeneic 4T1 mouse adenocarcinoma model, the chemopreventive model of chemically induced mammary carcinogenesis in rats, a cell antioxidant assay, and robust in vitro analyses using MCF-7 and MDA-MB-231 cancer cells. RESULTS: The dominant metabolites in the A. melanocarpa fruit peel extract tested were phenolic derivatives classified as anthocyanins and procyanidins. In a therapeutic model, aronia significantly reduced the volume of 4T1 tumors at both higher and lower doses. In the same tumors, we noted a significant dose-dependent decrease in the mitotic activity index compared to the control. In the chemopreventive model, the expression of Bax was significantly increased by aronia at both doses. Additionally, aronia decreased Bcl-2 and VEGF levels, increasing the Bax/Bcl-2 ratio compared to the control group. The cytoplasmic expression of caspase-3 was significantly enhanced when aronia was administered at a higher dosage, in contrast to both the control group and the aronia group treated with a lower dosage. Furthermore, the higher dosage of aronia exhibited a significant reduction in the expression of the tumor stem cell marker CD133 compared to the control group. In addition, the examination of aronia`s epigenetic impact on tumor tissue through in vivo analyses revealed significant alterations in histone chemical modifications, specifically H3K4m3 and H3K9m3, miRNAs expression (miR155, miR210, and miR34a) and methylation status of tumor suppressor genes (PTEN and TIMP3). In vitro studies utilizing a methanolic extract of A.melanocarpa demonstrated significant anti-cancer properties in the MCF-7 and MDA-MB-231 cell lines. Various analyses, including Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential, were conducted in this regard. Additionally, the aronia extract enhanced the responsiveness to epirubicin in both cancer cell lines. CONCLUSION: This study is the first to analyze the antitumor effect of A. melanocarpa in selected models of experimental breast carcinoma in vivo and in vitro. The utilization of the antitumor effects of aronia in clinical practice is still minimal and requires precise and long-term clinical evaluations. Individualized cancer-type profiling and patient stratification are crucial for effectively implementing plant nutraceuticals within targeted anti-cancer strategies in clinical oncology.

• Klíčová slova
• Aronia melanocarpa L., breast carcinoma, epigenetics, in vitro models, mechanism of action, rodent models,
• Publikační typ
• časopisecké články MeSH

Cancer causes many deaths worldwide each year, especially due to tumor heterogeneity leading to disease progression and treatment failure. Targeted treatment of heterogeneous population of cells - cancer stem cells is still an issue in protecting affected individuals against associated multidrug resistance and disease progression. Nanotherapeutic agents have the potential to go beyond state-of-the-art approaches in overall cancer management. Specially assembled nanoparticles act as carriers for targeted drug delivery. Several nanodrugs have already been approved by the US Food and Drug Administration (FDA) for treating different cancer types. Phytochemicals isolated from plants demonstrate considerable potential for nanomedical applications in oncology thanks to their antioxidant, anti-inflammatory, anti-proliferative, and other health benefits. Phytochemical-based NPs can enhance anticancer therapeutic effects, improve cellular uptake of therapeutic agents, and mitigate the side effects of toxic anticancer treatments. Per evidence, phytochemical-based NPs can specifically target CSCs decreasing risks of tumor relapse and metastatic disease manifestation. Therefore, this review focuses on current outlook of phytochemical-based NPs and their potential targeting CSCs in cancer research studies and their consideration in the framework of predictive, preventive, and personalized medicine (3PM).

• Klíčová slova
• cancer stem cells therapy, nanomedicine, nanoparticles, phytochemicals, plant-derived foods, predictive preventive personalized medicine, primary secondary tertiary care,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Thromboembolism is the third leading vascular disease, with a high annual incidence of 1 to 2 cases per 1000 individuals within the general population. The broader term venous thromboembolism generally refers to deep vein thrombosis, pulmonary embolism, and/or a combination of both. Therefore, thromboembolism can affect both - the central and peripheral veins. Arterial thromboembolism causes systemic ischemia by disturbing blood flow and oxygen supply to organs, tissues, and cells causing, therefore, apoptosis and/or necrosis in the affected tissues. Currently applied antithrombotic drugs used, e.g. to protect affected individuals against ischemic stroke, demonstrate significant limitations. For example, platelet inhibitors possess only moderate efficacy. On the other hand, thrombolytics and anticoagulants significantly increase hemorrhage. Contextually, new approaches are extensively under consideration to develop next-generation antithrombotics with improved efficacy and more personalized and targeted application. To this end, phytochemicals show potent antithrombotic efficacy demonstrated in numerous in vitro, ex vivo, and in vivo models as well as in clinical evaluations conducted on healthy individuals and persons at high risk of thrombotic events, such as pregnant women (primary care), cancer, and COVID-19-affected patients (secondary and tertiary care). Here, we hypothesized that specific antithrombotic and antiplatelet effects of plant-derived compounds might be of great clinical utility in primary, secondary, and tertiary care. To increase the efficacy, precise patient stratification based on predictive diagnostics is essential for targeted protection and treatments tailored to the person in the framework of 3P medicine. Contextually, this paper aims at critical review toward the involvement of specific classes of phytochemicals in antiplatelet and anticoagulation adapted to clinical needs. The paper exemplifies selected plant-derived drugs, plant extracts, and whole plant foods/herbs demonstrating their specific antithrombotic, antiplatelet, and fibrinolytic activities relevant for primary, secondary, and tertiary care. One of the examples considered is antithrombotic and antiplatelet protection specifically relevant for COVID-19-affected patient groups.

• Klíčová slova
• Anticoagulation, Antiplatelet effects, COVID-19, Circulation, Comorbidities, Health policy, Individualized patient profile, Ischemic stroke, Molecular pathways, Natural drugs, Phytochemicals, Predictive preventive personalized medicine, Primary, secondary, tertiary care, Targets, Therapeutic modalities, Thrombosis, Treated cancers, Vascular disease,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Breast cancer incidence is actually the highest one among all cancers. Overall breast cancer management is associated with challenges considering risk assessment and predictive diagnostics, targeted prevention of metastatic disease, appropriate treatment options, and cost-effectiveness of approaches applied. Accumulated research evidence indicates promising anti-cancer effects of phytochemicals protecting cells against malignant transformation, inhibiting carcinogenesis and metastatic spread, supporting immune system and increasing effectiveness of conventional anti-cancer therapies, among others. Molecular and sub-/cellular mechanisms are highly complex affecting several pathways considered potent targets for advanced diagnostics and cost-effective treatments. Demonstrated anti-cancer affects, therefore, are clinically relevant for improving individual outcomes and might be applicable to the primary (protection against initial cancer development), secondary (protection against potential metastatic disease development), and tertiary (towards cascading complications) care. However, a detailed data analysis is essential to adapt treatment algorithms to individuals' and patients' needs. Consequently, advanced concepts of patient stratification, predictive diagnostics, targeted prevention, and treatments tailored to the individualized patient profile are instrumental for the cost-effective application of natural anti-cancer substances to improve overall breast cancer management benefiting affected individuals and the society at large.

• Klíčová slova
• Breast cancer, COVID-19, Cost-effective disease management, Evidence-based research data, Food, Health risk assessment, Improved individual outcomes, Individualized patient profiling, Modifiable risk factors, Molecular patterns, Phytochemicals, Plants, Predictive Preventive Personalized Medicine (PPPM/3PM), Primary secondary tertiary care, Stroke, Translational research, Treated cancer,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Multi-factorial mitochondrial damage exhibits a "vicious circle" that leads to a progression of mitochondrial dysfunction and multi-organ adverse effects. Mitochondrial impairments (mitochondriopathies) are associated with severe pathologies including but not restricted to cancers, cardiovascular diseases, and neurodegeneration. However, the type and level of cascading pathologies are highly individual. Consequently, patient stratification, risk assessment, and mitigating measures are instrumental for cost-effective individualized protection. Therefore, the paradigm shift from reactive to predictive, preventive, and personalized medicine (3PM) is unavoidable in advanced healthcare. Flavonoids demonstrate evident antioxidant and scavenging activity are of great therapeutic utility against mitochondrial damage and cascading pathologies. In the context of 3PM, this review focuses on preclinical and clinical research data evaluating the efficacy of flavonoids as a potent protector against mitochondriopathies and associated pathologies.

• Klíčová slova
• anti-oxidant activity, cancer, cardiovascular disease, dysfunction, flavonoids, genoprotection, injury, mitochondrial function, mitochondrial impairment, mitochondriopathy, natural substances, neurodegeneration, patient stratification, phytochemicals, predictive preventive personalized medicine (PPPM/3PM), stress, tumorigenesis,
• MeSH
• antioxidancia farmakologie   terapeutické užití   MeSH
• cytoprotekce účinky léků   MeSH
• flavonoidy farmakologie   terapeutické užití   MeSH
• individualizovaná medicína metody   MeSH
• lidé MeSH
• mitochondriální nemoci diagnóza   prevence a kontrola   MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• mitofagie účinky léků   MeSH
• oxidační stres účinky léků   MeSH
• prognóza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antioxidancia MeSH
• flavonoidy MeSH

Cost-efficacy of currently applied treatments is an issue in overall cancer management challenging healthcare and causing tremendous economic burden to societies around the world. Consequently, complex treatment models presenting concepts of predictive diagnostics followed by targeted prevention and treatments tailored to the personal patient profiles earn global appreciation as benefiting the patient, healthcare economy, and the society at large. In this context, application of flavonoids as a spectrum of compounds and their nano-technologically created derivatives is extensively under consideration, due to their multi-faceted anti-cancer effects applicable to the overall cost-effective cancer management, primary, secondary, and even tertiary prevention. This article analyzes most recently updated data focused on the potent capacity of flavonoids to promote anti-cancer therapeutic effects and interprets all the collected research achievements in the frame-work of predictive, preventive, and personalized (3P) medicine. Main pillars considered are: - Predictable anti-neoplastic, immune-modulating, drug-sensitizing effects; - Targeted molecular pathways to improve therapeutic outcomes by increasing sensitivity of cancer cells and reversing their resistance towards currently applied therapeutic modalities.

• Klíčová slova
• Anthocyanidins, Anti-bacterial, Anti-cancer agents, Anti-inflammation, Anti-viral, COVID-19, Chalcones, Chemotherapy, Disease management, Drug-sensitizing effect, Flavanols, Flavanones, Flavones, Flavonoids, Flavonols, Health economy, Health policy, Immunotherapy, Isoflavonoids, Nano-carrier delivery, Phytochemicals, Predictive preventive personalized medicine (3PM/PPPM), Radiotherapy, Signalling pathways, Targeted therapy, Therapy efficacy, Therapy resistance,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Comprehensive scientific data provide evidence that isolated phytochemicals or whole plant foods may beneficially modify carcinogenesis. The aim of this study was to evaluate the oncostatic activities of Rhus coriaria L. (sumac) using animal models (rat and mouse), and cell lines of breast carcinoma. R. coriaria (as a powder) was administered through the diet at two concentrations (low dose: 0.1% (w/w) and high dose: 1 % (w/w)) for the duration of the experiment in a syngeneic 4T1 mouse and chemically-induced rat mammary carcinoma models. After autopsy, histopathological and molecular analyses of tumor samples in rodents were performed. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were conducted. The dominant metabolites present in tested R. coriaria methanolic extract were glycosides of gallic acid (possible gallotannins). In the mouse model, R. coriaria at a higher dose (1%) significantly decreased tumor volume by 27% when compared to controls. In addition, treated tumors showed significant dose-dependent decrease in mitotic activity index by 36.5% and 51% in comparison with the control group. In the chemoprevention study using rats, R. coriaria at a higher dose significantly reduced the tumor incidence by 20% and in lower dose non-significantly reduced tumor frequency by 29% when compared to controls. Evaluations of the mechanism of oncostatic action using valid clinical markers demonstrated several positive alterations in rat tumor cells after the treatment with R. coriaria. In this regard, histopathological analysis of treated tumor specimens showed robust dose-dependent decrease in the ratio of high-/low-grade carcinomas by 66% and 73% compared to controls. In treated rat carcinomas, we found significant caspase-3, Bax, and Bax/Bcl-2 expression increases; on the other side, a significant down-regulation of Bcl-2, Ki67, CD24, ALDH1, and EpCam expressions and MDA levels. When compared to control specimens, evaluation of epigenetic alterations in rat tumor cells in vivo showed significant dose-dependent decrease in lysine methylation status of H3K4m3 and H3K9m3 and dose-dependent increase in lysine acetylation in H4K16ac levels (H4K20m3 was not changed) in treated groups. However, only in lower dose of sumac were significant decreases in the expression of oncogenic miR210 and increase of tumor-suppressive miR145 (miR21, miR22, and miR155 were not changed) observed. Finally, only in lower sumac dose, significant decreases in methylation status of three out of five gene promoters-ATM, PTEN, and TIMP3 (PITX2 and RASSF1 promoters were not changed). In vitro evaluations using methanolic extract of R. coriaria showed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). In conclusion, sumac demonstrated significant oncostatic activities in rodent models of breast carcinoma that were validated by mechanistic studies in vivo and in vitro.

• Klíčová slova
• MCF-7 cells, MDA-MB-231 cells, Rhus coriaria, angiogenesis, apoptosis, breast cancer, cancer stem cells, cell proliferation, epigenetics, mouse, rat, sumac,
• MeSH
• apoptóza MeSH
• buněčný cyklus MeSH
• fytogenní protinádorové látky farmakologie   MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• myši inbrední BALB C MeSH
• myši nahé MeSH
• myši MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorové buňky kultivované MeSH
• nádory prsu farmakoterapie   metabolismus   patologie   MeSH
• potkani Sprague-Dawley MeSH
• proliferace buněk MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• Rhus chemie   MeSH
• rostlinné extrakty farmakologie   MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fytogenní protinádorové látky MeSH
• mikro RNA MeSH
• nádorové biomarkery MeSH
• rostlinné extrakty MeSH

In the early twenty-first century, societies around the world are facing the paradoxal epidemic development of PCa as a non-communicable disease. PCa is the most frequently diagnosed cancer for men in several countries such as the USA. Permanently improving diagnostics and treatments in the PCa management causes an impressive divergence between, on one hand, permanently increasing numbers of diagnosed PCa cases and, on the other hand, stable or even slightly decreasing mortality rates. Still, aspects listed below are waiting for innovate solutions in the context of predictive approaches, targeted prevention and personalisation of medical care (PPPM / 3PM).A.PCa belongs to the cancer types with the highest incidence worldwide. Corresponding economic burden is enormous. Moreover, the costs of treating PCa are currently increasing more quickly than those of any other cancer. Implementing individualised patient profiles and adapted treatment algorithms would make currently too heterogeneous landscape of PCa treatment costs more transparent providing clear "road map" for the cost saving.B.PCa is a systemic multi-factorial disease. Consequently, predictive diagnostics by liquid biopsy analysis is instrumental for the disease prediction, targeted prevention and curative treatments at early stages.C.The incidence of metastasising PCa is rapidly increasing particularly in younger populations. Exemplified by trends observed in the USA, prognosis is that the annual burden will increase by over 40% in 2025. To this end, one of the evident deficits is the reactive character of medical services currently provided to populations. Innovative screening programmes might be useful to identify persons in suboptimal health conditions before the clinical onset of metastasising PCa. Strong predisposition to systemic hypoxic conditions and ischemic lesions (e.g. characteristic for individuals with Flammer syndrome phenotype) and low-grade inflammation might be indicative for specific phenotyping and genotyping in metastasising PCa screening and disease management. Predictive liquid biopsy tests for CTC enumeration and their molecular characterisation are considered to be useful for secondary prevention of metastatic disease in PCa patients.D.Particular rapidly increasing PCa incidence rates are characteristic for adolescents and young adults aged 15-40 years. Patients with early onset prostate cancer pose unique challenges; multi-factorial risks for these trends are proposed. Consequently, multi-level diagnostics including phenotyping and multi-omics are considered to be the most appropriate tool for the risk assessment, prediction and prognosis. Accumulating evidence suggests that early onset prostate cancer is a distinct phenotype from both aetiological and clinical perspectives deserving particular attention from view point of 3P medical approaches.

• Klíčová slova
• 3PM), Adapted treatment algorithms, Adolescence, Aetiology, Age, Aggressive metastatic disease, Alcohol consumption, Androgen dependent, Apoptosis resistance, Biomarker patterns, Body mass index BMI, Bone-specific alkaline phosphatase, C-index, Castration resistant, Choline, Circulating tumour cells (CTC), Coffee, Comorbidities, Curcumin, Diet, Disease manifestation, Economy, Elderly, Ellargic acid, Ethics, Ethnicity, Family history, Fish, Folate, Fruits, Garlic, Genetic, Green tea, Gut microbiota, Human development index, Hybrid imaging, Incidence, Indicator, Individualised patient profile, Inflammation, Insulin-like growth factor, Ischemic lesions, Lactate dehydrogenase, Life quality, Lifestyle, Liquid biopsy, Lycopene, Malignancy, Meat, Microcirculation, Modifiable risk factors, Mortality, Multi-factorial systemic disease, Multi-omics, Multi-parametric analysis, Obesity, Oxidative stress, PET/MRI, PSA screening, Patient stratification, Personalised nutrition, Physical activity, Prebiotics, Predictive preventive personalised medicine (PPPM, Probiotics, Prognosis, Prostate cancer (PCa), Prostate cancer antigen 3, Quercetin, Race, Radical prostatectomy, Risk assessment, Roadmap, Saturated fat, Selenium/selenite, Sexually transmitted diseases, Sleep disorders, Smoking, Socio-economic factors, Stillbenes, Sulphorapane, Survival, Systemic hypoxic condition, Toxic environment, Trace elements, Transrectal ultrasound, Trends, Urinary tract infection, Urology, Vasectomy, Vegetables, Vitamins A, C, D, E, and K, Young population, miRNA,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH